Efficacy and Safety of Intraoperative Hyperthermic Intraperitoneal Chemotherapy for Locally Advanced Colon Cancer
Authors: Alvaro Arjona-Sánchez, Esther Espinosa-Redondo, Alberto Gutiérrez-Calvo, Juan J. Segura-Sampedro, Estibalitz Pérez-Viejo, Vanessa Concepción-Martín, Susana Sánchez-García, Alfonso García-Fadrique, Isabel Prieto-Nieto, Pedro Barrios-Sanchez, Juan Torres-Melero, Maria Ramírez Faraco, Arancha Prada-Villaverde, Joaquin Carrasco-Campos, Manuel Artiles-Armas, Pedro Villarejo-Campos, Gloria Ortega-Pérez, Emrique Boldo-Roda, Juan-Manuel Sánchez-Hidalgo, Angela Casado-Adam, Lidia Rodríguez-Ortiz, Enrique Aranda, Maria Teresa Cano-Osuna, Cesar Díaz-López, Antonio Romero-Ruiz, Javier Briceño-Delgado, Sebastian Rufián-Peña, Miguel A. Lorenzo Liñán, Isabel M. Gallarín Salamanca, Marta Gónzalez Cordero, Isabel Ramos, Oriol Crusellas Maña, Araceli Mayol Oltra, Melissa Granados Rodríguez, Mari C. Vázquez Borrego, Auxiliadora Gómez España, Rosa M. Ortega Salas, Ana Martínez López, Carlos Villar, Cruces Garzas Martín de Almagro, Francisco Triviño Tarradas, Eva M. Torres Tordera, Blanca Rufián Andujar, Francisca Valenzuela Molina, Antonio Gordon Suarez, Francisco J. Medina Fernández, Manuel Diéz Alonso, Pilar Hernández Juara, Raquel Molina Villaverde, Carolina Castillo Torres, Jose I. Busteros Moraza, Inmaculada Lasa Unzué, Remedios Gómez Sanz, Alberto López García, María A. Heras Garceau, Ángel Serrano del Moral, Israel Manzanedo, Fernando Pereira, Santiago González Moreno, Alberto Titos García, Pedro A. Parra Baños, Milagros Carrasco Prats, Miguel Ruíz Marín, Emilio Terol Garaulet, Francisco García Molina, Rafael Morales Soriano, Cristina Pineño Flores, Raquel Pérez Rodríguez, Carolina Hernández Pérez, Ruth Afonso Gómez, María Micaela Viña Romero, Amelia Muñoz Hernández, Victoria Castro López-Tarruella, Modesto E. Moneva Arce, Rajesh Gianchandani Moorjani, Juan M. Sánchez González, Carmen Díaz López, Guillermo Hernández Hernández, José G. Díaz Mejías, Moisés J. Hernández Barroso, None Abreu Falcon
Journal: JAMA Surgery (2023)

Importance Peritoneal metastasis in patients with locally advanced colon cancer (T4 stage) is estimated to recur at a rate of approximately 25% at 3 years from surgical resection and is associated with poor prognosis. There is controversy regarding the clinical benefit of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. Objective To assess the efficacy and safety of intraoperative HIPEC in patients with locally advanced colon cancer. Design, Setting, and Participants This open-label, phase 3 randomized clinical trial was conducted in 17 Spanish centers from November 15, 2015, to March 9, 2021. Enrolled patients were aged 18 to 75 years with locally advanced primary colon cancer diagnosed preoperatively (cT4N02M0). Interventions Patients were randomly assigned 1:1 to receive cytoreduction plus HIPEC with mitomycin C (30 mg/m 2 over 60 minutes; investigational group) or cytoreduction alone (comparator group), both followed by systemic adjuvant chemotherapy. Randomization of the intention-to-treat population was done via a web-based system, with stratification by treatment center and sex. Main Outcomes and Measures The primary outcome was 3-year locoregional control (LC) rate, defined as the proportion of patients without peritoneal disease recurrence analyzed by intention to treat. Secondary end points were disease-free survival, overall survival, morbidity, and rate of toxic effects. Results A total of 184 patients were recruited and randomized (investigational group, n = 89; comparator group, n = 95). The mean (SD) age was 61.5 (9.2) years, and 111 (60.3%) were male. Median duration of follow-up was 36 months (IQR, 27-36 months). Demographic and clinical characteristics were similar between groups. The 3-year LC rate was higher in the investigational group (97.6%) than in the comparator group (87.6%) (log-rank P = .03; hazard ratio [HR], 0.21; 95% CI, 0.05-0.95). No differences were observed in disease-free survival (investigational, 81.2%; comparator, 78.0%; log-rank P = .22; HR, 0.71; 95% CI, 0.41-1.22) or overall survival (investigational, 91.7%; comparator, 92.9%; log-rank P = .68; HR, 0.79; 95% CI, 0.26-2.37). The definitive subgroup with pT4 disease showed a pronounced benefit in 3-year LC rate after investigational treatment (investigational: 98.3%; comparator: 82.1%; log-rank P = .003; HR, 0.09; 95% CI, 0.01-0.70). No differences in morbidity or toxic effects between groups were observed. Conclusions and Relevance In this randomized clinical trial, the addition of HIPEC to complete surgical resection for locally advanced colon cancer improved the 3-year LC rate compared with surgery alone. This approach should be considered for patients with locally advanced colorectal cancer. Trial Registration ClinicalTrials.gov Identifier: NCT02614534